Neoadjuvant darolutamide plus androgen deprivation therapy for high-risk and locally advanced prostate cancer: a multicenter, open-label, single-arm, phase II trial.

Propose: This study aimed to evaluate the efficacy and safety of neoadjuvant treatment of darolutamide, a next-generation androgen receptor inhibitor, plus androgen deprivation therapy (ADT) for patients with locally advanced prostate cancer (LAPC).

Methods: This single-arm, multicenter, open-label phase II trial (ClinicalTrials.gov: NCT05249712, 2022-01-01), recruited 30 localized high-risk/very high-risk prostate cancer (HRPCa/VHRPCa) patients from three centers in China between 2021 and 2023. Following six months of neoadjuvant therapy combining darolutamide with ADT, the patients underwent radical prostatectomy (RP). The primary endpoint is pathologic complete response (pCR) or minimal residual disease (MRD). The secondary endpoints are progression-free survival (PFS), positive surgical margin rate and safety. Exploratory endpoint was the relationship between postoperative ctDNA and primary outcome.

Results: The pCR or MRD rate was 40%(n = 12). Only four patients (13.3%) had positive surgical margins. The 12 months PFS was 90.0% (95% CI, 74.4-96.5%). The detection of circulating tumor DNA (ctDNA) accurately predicts the disease progression. No grade 3 or 4 adverse events were observed. The most frequent adverse events included hot flashes and elevated alanine aminotransferase or aspartate transaminase levels, which were observed in three patients (10%).

Conclusion: Neoadjuvant therapy with darolutamide plus ADT for six months followed by RP is effective and safe for HRPCa and LAPC. The detection of ctDNA can predict disease progression.